Tosylchloramide sodium

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

19 November 1990 - 22 November 1990

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Test was performed under GLP and according to OECD 405 guideline.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1991

Report date:

1991

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Tosylchloramide sodium

EC Number:

204-854-7

EC Name:

Tosylchloramide sodium

Cas Number:

127-65-1

Molecular formula:

(C7H4SO2NCl)Na

IUPAC Name:

sodium chloro(4-methylbenzenesulfonyl)azanide

Details on test material:

Indetification: Halamid
Description: White powder
Batch: 9520830
Purity: Technically pure, treated as 100% pure
Instructions for test substance storage: In the closed container at room temperature (keep cool) and in the dark.
Stability under storage conditions: Stable

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Broekman Institute, Someren, The Netherlands.
- Age at study initiation: approximately 14 weeks
- Weight at study initiation: 2395 grams
- Housing: Individually in cages with perforated floors
- Diet (e.g. ad libitum): Standard laboratory rabbit diet (LKK-20, pellet diameter 4 mm, Hope Farms, Woerden, The Netherlands) approx. 100 g per day.
- Water (e.g. ad libitum): Free access to tap-water diluted with decalcified water.
- Acclimation period: At least five days before start of treatment under test conditions

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21
- Humidity (%): 55
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: 19 November 1990 - 22 November 1990

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: the untreated eye

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1g

Duration of treatment / exposure:

72 hour

Observation period (in vivo):

72 hours

Number of animals or in vitro replicates:

1

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no

SCORING SYSTEM: According to Draize
Scoring system eye irritation

Cornea: degree of density (area most dense taken for reading)
0 No ulceration or opacity
1 Scattered or diffuse areas of opacity (other than slight dulling of normal lustre), details of iris clearly visible
2 Easily discernible translucent areas, details of iris slightly obscured
3 Nacrous areas, no details of iris visible, size of pupil barely discernible
4 Opaque cornea, iris not discernible through the opacity

Area of Cornea Involved
1 One quarter (or less) but not zero
2 Greater than one quarter but less than half
3 Greater than half but less than three quarters
4 Greater than three quarters, up to whole area

Iris
0 Normal
1 Markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperaemia or injection, any of these or combination of any thereof, iris still reacting to light (sluggish reaction is positive)
2 No reaction to light, haemorrhage, gross destruction (any or all of these)

Conjunctivae
Redness (refers to palpebral and bulbar conjunctivae cornea and iris)

0 Blood vessels normal
1 Some blood vessels definitely hyperaemic
(injected)
2 Diffuse, crimson colour, individual vessels not easily discernible
3 Diffuse, beefy red

Chemosis (lids and/or nictitating membranes)
0 No swelling 0
1 Any swelling above normal (includes nictitating membranes)
2 Obvious swelling with partial eversion of lids
3 Swelling with lids about half-closed
4 Swelling with lids more than half-closed

Discharge
0 No discharge
1 Any amount different from normal (does not include small amounts observed in inner canthus of normal animals)
2 Discharge with moistening of the lids and hairs just adjacent to lids
3 Discharge with moistening of the lids and hairs a considerable area around the eye

TOOL USED TO ASSESS SCORE: hand-slit lamp

On day 1, prior to test substance administration, the animal was physically examined and the eyes found to be normal. The test substance (approx. 100 mg per animal) was instilled in the conjunctival sac of the left eye of the animal after gently pulling the lower lid away from the eyeball. The lids were then gently held together for about one second to prevent loss of the test substance. The other eye remained untreated and served as the reference control. Immediately after the 24 hours observation, a solution of 2% fluorescein in water (adjusted to pH 7.0) was applied to both eyes of the animal to quantitatively examine the potential for corneal injury. This procedure was repeated on day 4. Any bright green stained area, indicating epithelial damage, was estimated as a percentage of the total corneal area.

Viability/Mortality; Daily, animal was also examined For signs of toxicity.
Body Weights: Day 1 of test (application day).
Symptoms: The eyes of the animal were examined approximately 1, 24, 48 and 72 hours after instillation of the test substance. The corrosive properties of the test substance were described and recorded.

Results and discussion

In vivo

Results

Irritation parameter:

overall irritation score

Remarks:

Cornea/iris/conjuctivae (excluding area and discharge not relevant for C&L)

Basis:

animal #1

Time point:

24/48/72 h

Score:

3.3

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: Due to the severity fo the effects the study was terminated after 72 hours

Irritant / corrosive response data:

Instillation of HALAMID into one of the eyes of animal 351 affected the cornea, iris and conjunctivae. The eye effects consisted of severe corneal opacity and severe conjunctival redness and chemosis. Effects on the iris could not be observed after day 1, due to the severe corneal opacity. Therefore the study was terminated on day 4. No further animals were treated.
Treatment of the eyes with 2% fluorescein, 24 and 72 hours after test substance instillation revealed corneal epithelial damage in animal 351. There was clear evidence of ocular corrosion.

Other effects:

No toxic symptoms were observed in the animal during the test period and no mortality occurred.

Any other information on results incl. tables

Rabbit No and sex	Region of the eye			Hours after instillation				Average 24-48 hours
				1	24	48	72
3068 f	Cornea	Degree of opacity		3	4	4	4	4
		Area of opacity		2	2	2	2	2
	Iris			1	-	-	-	-
	Conjunctivae		Redness	3	3	3	3	3
			Chemosis	3	3	3	3	3
			Discharge	0	0	1	3	1.3

* Due to the severity of the effects the study was terminated after 72 hours.

1 Iris could be scored for only approx. 25%, therefore no pupil reaction to light could be assessed.  Lacrimation was observed. Grey/white discolouration of the conjunctivae.

24 Iris could not be scored due to corneal opacity.  Lacrimation was observed. Grey/white discolouration of the conjunctivae. Fluor. area 100%.

48 Iris could not be scored due to corneal opacity.  Lacrimation was observed. Grey/white discolouration of the conjunctivae.

72 Iris could not be scored due to corneal opacity.  Grey/white discolouration of the conjunctivae. Fluor. area 100%.

Conjunctival redness and chemosis were also observed on the outside of the eyelids on days 2, 3 and 4.

Applicant's summary and conclusion

Interpretation of results:

other: Eye Dam. 1

Remarks:

according to the classification criteria outlined in Annex I of 1272/2008/EC (CLP)

Conclusions:

Due to the severity of the effects observed in one eye of the test animal the test substance is classified as Eye Dam. category 1 (irreversible effects on the eye) according to the classification criteria outlined in Annex I of 1272/2008/EC (CLP).

Executive summary:

The purpose of this study was to assess the possible irritation or corrosion potential when a single dose of Tosylchloramide sodium, trihydrate was placed i n the conjunctival sac of a rabbit eye. This study was carried out in accordance with OECD Guideline No. 405, "Acute Eye Irritation/Corrosion" and EEC Directive 84/449/EEC, Part B.5, Acute Toxicity - Eye Irritation. Tosylchloramide sodium, trihydrate was instilled in one of the eyes of one animal, followed by four observations at approximately 1, 24, 48 and 72 hours after test article administration. Only one animal was used, due to the irritancy obtained in the skin irritation study and the animal in this eye irritation study. Under the conditions of this study, Tosylchloramide sodium, trihydrate resulted in adverse effects of the cornea, iris and the conjunctivae. The eye effects consisted of severe corneal opacity and severe conjunctival redness and chemosis. Effects on the iris could not be observed after day 1, due to the corneal opacity. Therefore the study was terminated on day 4. No further animals were treated. Clear ocular corrosion was observed in the single animal. No signs of systemic intoxication were observed during the study period.

Due to the severity of the effects observed in one eye of the test animal the test substance is classified as Eye Dam. category 1 (H318 Causes serious eye damage ) according to according to the classification criteria outlined in Annex I of 1272/2008/EC (CLP).